Estimation of Injury Limits at Vulnerable Impact Locations Along the Forearm Via THUMS AM50 Finite Element Model at Airbag Loading Rates.

Side and frontal airbag deployment represents the main injury mechanism to the upper extremity during automotive collisions. Previous dynamic injury limit research has been limited to testing the forearm at either the assumed most vulnerable location to fracture, the distal 1/3rd, or the midpoint. Studies have varied the surface to which impacts were applied, with no clear consensus on the site of greatest vulnerability. The unpredictability of airbag impact location, especially with altered hand positioning, limits the effectiveness of existing forearm injury limits determined from impacts at only one location. The current study quantified the effect of impacts at alternative locations on injury risk along the forearm using the THUMS FE model. Airbag-level impacts were simulated along the forearm on all four anatomical surfaces. Results showed the distal 1/3rd is not the most vulnerable location (for any side), indicating forearm fracture is not solely driven by area moment of inertia (as previously assumed). The posterior forearm was the weakest, suggesting that current test standards underestimate the fracture risk of the forearm. Linear regression models showed strong correlation between forearm fracture risk and bone geometry (cross-sectional area and area moment of inertia) as well as soft-tissue depth, potentially providing the ability to predict forearm injury tolerances for any location or forearm size. This study demonstrated the forearm's vulnerability to fracture from airbag deployments, indicating the need for safety systems to better address injury mechanisms for the upper limb to effectively protect drivers.

Activation of TNF Receptor 2 Improves Synaptic Plasticity and Enhances Amyloid-ß Clearance in an Alzheimer's Disease Mouse Model with Humanized TNF Receptor 2.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a master cytokine involved in a variety of inflammatory and neurological diseases, including Alzheimer's disease (AD). Therapies that block TNF-α proved ineffective as therapeutic for neurodegenerative diseases, which might be explained by the opposing functions of the two receptors of TNF (TNFRs): while TNFR1 stimulation mediates inflammatory and apoptotic pathways, activation of TNFR2 is related to neuroprotection. Despite the success of targeting TNFR2 in a transgenic AD mouse model, research that better mimics the human context is lacking. OBJECTIVE: The aim of this study is to investigate whether stimulation of TNFR2 with a TNFR2 agonist is effective in activating human TNFR2 and attenuating AD neuropathology in the J20xhuTNFR2-k/i mouse model. METHODS: Transgenic amyloid-ß (Aß)-overexpressing mice containing a human extracellular TNFR2 domain (J20xhuTNFR2-k/i) were treated with a TNFR2 agonist (NewStar2). After treatment, different behavioral tests and immunohistochemical analysis were performed to assess different parameters, such as cognitive functions, plaque deposition, synaptic plasticity, or microglial phagocytosis. RESULTS: Treatment with NewStar2 in J20xhuTNFR2-k/i mice resulted in a drastic decrease in plaque load and beta-secretase 1 (BACE-1) compared to controls. Moreover, TNFR2 stimulation increased microglial phagocytic activity, leading to enhanced Aß clearance. Finally, activation of TNFR2 rescued cognitive impairments and improved synaptic plasticity. CONCLUSION: Our findings demonstrate that activation of human TNFR2 ameliorates neuropathology and improves cognitive functions in an AD mouse model. Moreover, our study confirms that the J20xhuTNFR2-k/i mouse model is suitable for testing human TNFR2-specific compounds.

Study on the Influence of Selected Fabrics and Stitching on the Strength of Upholstery Covers.

So far, no coherent and comprehensive method has been elaborated allowing investigation of tensile strength of upholstery seams dedicated to upholstered furniture. Producers of this type of furniture are interested in the assessment of the quality of upholstery material joints, which seems to be particularly important for ensuring the appropriate quality of products. Therefore, the objective of this research was to investigate the influence of the type of material used and the direction of the fabric cut on the strength of upholstery covers. Static tensile testing of selected upholstery fabric samples was performed, and an attempt was made to identify the most optimal fabric-seam joints. It was stated as a conclusion that the fabric tensile strength was the highest for Secret 10 fabric. In addition, the strength of upholstery covers is not influenced by the direction of the fabric die cut. For each fabric, a different configuration is preferable, as shown by results (Power 13: A-B, Secret 10: B-B, Soft 10: A-A). The method, implemented for upholstered furniture, allows for an objective assessment of the strength of upholstery covers and the selection of the most advantageous fabric-seam combination for future furniture designs.

Quantification of Behind Shield Blunt Impacts Using a Modified Upper Extremity Anthropomorphic Test Device.

Ballistic shields are used by military and police members in dangerous situations to protect the user against threats such as gunfire. When struck, the shield material deforms to absorb the incoming kinetic energy of the projectile. If the rapid back-face deformation contacts the arm, it can potentially impart a large force, leading to injury risk, termed behind armor blunt trauma (BABT). This work characterized the loading profiles due to the contact between the deforming back-face of the shield and the arm using a modified upper extremity anthropomorphic test device (ATD). This ATD measured forces at the hand, wrist, forearm, and elbow to compare the locational effects of the force transfer for future investigations of fracture risk. Two composite ballistic shields, both with the same ballistic protection rating, were investigated and had statistically different responses to the same impact conditions, indicating a further need for shield safety evaluation. Additionally, ballistic force curves were compared among stand-off distances, defined as the distance between the back-face of the shield and the front of the force sensor, where the peak impact force significantly decreased with increased stand-off. This study presents the first highly instrumented ATD upper limb capable of evaluating BABT and characterization of these loading profiles. This work demonstrates the importance of realistic boundary conditions as loading varies by anatomical location. Stand-off distance is an effective method to reduce loading and should be considered in future shield design iterations and standards that are developed using this device.

The Axial Impact Response and Plantar Load Distribution of the Hybrid III and Military Lower Extremity Under Altered Ankle Postures.

Foot injuries as a result of automotive collisions are frequent and impactful. Anthropomorphic test devices (ATDs), used to assess injury risk during impact scenarios such as motor vehicle collisions, typically assess risk of foot/ankle injuries by analyzing data in tibia load cells. The peak axial force and the tibia index are metrics commonly used to evaluate risk of injury to the lower extremity but do not directly account for injury risk to the foot, or the risk of injury associated with out-of-position loading. Two ATDs, the Hybrid III lower leg and the Military Lower Extremity, were exposed to axial impacts at seven different ankle postures. An array of piezoresistive sensors located on the insole of a boot was employed during these tests to assess the load distribution variations among postures and between ATD models on the plantar surface of the foot. Both posture and ATD model affected the load distribution on the foot, highlighting the need for regional injury risk assessments in this vulnerable anatomical region. The increase in forefoot loading during plantarflexion was not reflected in the standard industry metrics of peak axial force or tibia index, suggesting that increased fracture risk to the forefoot would not be detected. The variations in load distribution between the models could also alter injury risk assessment in frontal collisions based on differences in attenuation. These data could be used for regional foot injury assessment and to inform the design of an improved ATD foot.

Aerosol emission in professional singing of classical music.

In this study, emission rates of aerosols emitted by professional singers were measured with a laser particle counter under cleanroom conditions. The emission rates during singing varied between 753 and 6093 particles/sec with a median of 1537 particles/sec. Emission rates for singing were compared with data for breathing and speaking. Significantly higher emission rates were found for singing. The emission enhancements between singing and speaking were between 4.0 and 99.5 with a median of 17.4, largely due to higher sound pressure levels when singing. Further, significant effects of vocal loudness were found, whereas there were no significant differences between the investigated voice classifications. The present study supports the efforts to improve the risk management in cases of possible aerogenic virus transmission, especially for choir singing.

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

Aerosol emission of adolescents voices during speaking, singing and shouting.

Since the outbreak of the COVID-19 pandemic, singing activities for children and young people have been strictly regulated with far-reaching consequences for music education in schools and ensemble and choir singing in some places. This is also due to the fact, that there has been no reliable data available on aerosol emissions from adolescents speaking, singing, and shouting. By utilizing a laser particle counter in cleanroom conditions we show, that adolescents emit fewer aerosol particles during singing than what has been known so far for adults. In our data, the emission rates ranged from 16 P/s to 267 P/s for speaking, 141 P/s to 1240 P/s for singing, and 683 P/s to 4332 P/s for shouting. The data advocate an adaptation of existing risk management strategies and rules of conduct for groups of singing adolescents, like gatherings in an educational context, e.g. singing lessons or choir rehearsals.

Biomechanical Aspects of Actin Bundle Dynamics.

Lamellipodial and filopodial protrusions are two of the main aggregate types of filamentous actin in living cells. Even though filopodia are essential to a range of vital cell functions, the mechanisms leading to their formation are still debated. Filopodia are relatively stiff and rod-like structures that are embedded in the highly dynamic framework of the backward flowing meshwork of the lamellipodium. Phenomena such as lateral filopodia drift and collision events suggest that mechanical aspects play a significant role in filopodia dynamics. In this paper, we systematically analyze the interplay between the backward flow of actin in the lamellipodium and the drift velocity of actin bundles, that we identify to be filopodia, in a quantitative manner in cells of given morphology and controlled myosin activity. Moreover, we study mechanical aspects of fusion of actin bundles drifting laterally in the lamellipodium. We find that the dynamics of actin bundles drift and fusion can be captured in a mechanical framework, which leads to a model of actin bundles orientation.

A Force-Sensing Insole to Quantify Impact Loading to the Foot.

Lower leg injuries commonly occur in frontal automobile collisions, and are associated with high disability rates. Accurate methods to predict these injuries must be developed to facilitate the testing and improvement of vehicle safety systems. Anthropomorphic test devices (ATDs) are often used to assess injury risk by mimicking the behavior of the human body in a crash while recording data from sensors at discrete locations, which are then compared to established safety limits developed by cadaveric testing. Due to the difference in compliance of cadaveric and ATD legs, the force dissipating characteristics of footwear, and the lack of direct measurement of injury risk to the foot and ankle, a novel instrumented insole was developed that could be applied equally to all specimens both during injury limit generation and during safety evaluation tests. An array of piezoresistive sensors were calibrated over a range of speeds using a pneumatic impacting apparatus, and then applied to the insole of a boot. The boot was subsequently tested and compared to loads measured using ankle and toe load cells in an ATD, and found to have an average error of 10%. The sensors also provided useful information regarding the force distribution across the sole of the foot during an impact, which may be used to develop regional injury criteria. This work has furthered the understanding of lower leg injury prediction and developed a tool that may be useful in developing accurate injury criteria in the future for the foot and lower leg.

Amyloid blood biomarker detects Alzheimer's disease.

Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers or expensive such as positron emission tomography (PET) scanning. Here, we determine the secondary structure change of amyloid-ß (Aß) in human blood. This change used as blood amyloid biomarker indicates prodromal AD and correlates with CSF AD biomarkers and amyloid PET imaging in the cross-sectional BioFINDER cohort. In a further population-based longitudinal cohort (ESTHER), the blood biomarker detected AD several years before clinical diagnosis in baseline samples with a positive likelihood ratio of 7.9; that is, those who were diagnosed with AD over the years were 7.9 times more likely to test positive. This assay may open avenues for blood screening of early AD stages as a funnel for further more invasive and expensive tests.

Resident Access to the St. Louis County Prescription Drug Monitoring Program: Why PDMPs Matter and How to Gain Access.

Prescription Drug Monitoring Programs (PDMPSs) permit physicians to determine whether patients obtained addictive substances from multiple physicians or pharmacies. In April 2017, the Saint Louis County Department of Public Health created its own PDMP. This manuscript evaluates evidence regarding the efficacy of PDMPs, in addition to discussing their impact on patient care and a provider's workflow. It also details how physicians can register to use the St. Louis County PDMP, Missouri's de-facto PDMP.

Prevalence and outcome of late-onset seizures due to autoimmune etiology: A prospective observational population-based cohort study.

OBJECTIVE: The increasing incidence of new-onset seizures with age is well known. Often, the etiology cannot be clarified. In the present study, patients with unprovoked late-onset seizures and without known neoplasm, who might have had paraneoplastic encephalitis, were investigated for a potentially underlying autoimmunity. METHODS: Sixty-six consecutive patients (36 women; aged ≥55 years) after having at least one seizure or seizures for ≤6 months were prospectively identified over a period of 4.75 years. All patients were tested for serum and cerebrospinal fluid (CSF) antibodies (Abs) to both neural cell-surface and intracellular antigens. Forty-five (68%) underwent brain magnetic resonance imaging (MRI). Follow-up in Ab-positive cases was ≥6 months. RESULTS: Two patients had high titers of anti-CASPR2 (contactin-associated protein-like 2) Abs in serum and CSF and fulfilled the diagnostic criteria of definite limbic encephalitis. Another two patients had bilateral encephalitic temporal MRI abnormalities. They also satisfied the criteria of definite limbic encephalitis, even though they had no Abs in serum or CSF. All four were in the age range of 55-70 years. They received immunotherapy and/or antiepileptic drug treatment and became seizure-free. SIGNIFICANCE: Our findings suggest that autoimmunity should be considered an important etiology in patients with late-onset seizures. Testing for neural antibodies and brain MRI may be worthwhile in this patient group.

An ATR-FTIR Sensor Unraveling the Drug Intervention of Methylene Blue, Congo Red, and Berberine on Human Tau and Aß.

Alzheimer's disease affects millions of human beings worldwide. The disease progression is characterized by the formation of plaques and neurofibrillary tangles in the brain, which are based on aggregation processes of the Aß peptide and tau protein. Today there is no cure and even no in vitro assay available for the identification of drug candidates, which provides direct information concerning the protein secondary structure label-free. Therefore, we developed an attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) sensor, which uses surface bound antibodies to immobilize a desired target protein. The secondary structure of the protein can be evaluated based on the secondary structure sensitive frequency of the amide I band. Direct information about the effect of a drug candidate on the secondary structure distribution of the total target protein fraction within the respective body fluid can be detected by a frequency shift of the amide I band. Thereby, the extent of the amide I shift is indicative for the compound efficiency. The functionality of this approach was demonstrated by the quantification of the effect of the drug candidate methylene blue on the pathogenic misfolded tau protein as extracted from cerebrospinal fluid (CSF). Methylene blue induces a shift from pathogenic folded ß-sheet dominated to the healthy monomeric state. A similar effect was observed for congo red on pathogenic Aß isoforms from CSF. In addition, the effect of berberine on synthetic Aß1-42 is studied. Berberine seems to decelerate the aggregation process of synthetic Aß1-42 peptides.

Disruptive colouration in reef fish: does matching the background reduce predation risk?

Animals use disruptive colouration to prevent detection or recognition by potential predators or prey. Highly contrasting elements within colour patterns, including vertical or horizontal bars, are thought to be effective at distracting attention away from body form and reducing detection likelihood. However, it is unclear whether such patterns need to be a good match to the spatial characteristics of the background to gain cryptic benefits. We tested this hypothesis using the iconic vertically barred humbug damselfish, Dascyllus aruanus (Linneaus 1758), a small reef fish that lives among the finger-like projections of branching coral colonies. Using behavioural experiments, we demonstrated that the spatial frequency of the humbug pattern does not need to exactly match the spatial frequency of the coral background to reduce the likelihood of being attacked by two typical reef fish predators: slingjaw wrasse, Epibulus insidiator (Pallas 1770), and coral trout, Plectropomus leopardus (Lacépède 1802). Indeed, backgrounds with a slightly higher spatial frequency than the humbug body pattern provided more protection from predation than well-matched backgrounds. These results were consistent for both predator species, despite differences in their mode of foraging and visual acuity, which was measured using anatomical techniques. We also showed that a slight mismatch in the orientation of the vertical bars did not increase the chances of detection. However, the likelihood of attack did increase significantly when the bars were perpendicular to the background. Our results provide evidence that fish camouflage is more complex than it initially appears, with likely many factors influencing the detection likelihood of prey by relevant predators.

Predicting psychotherapy outcome based on therapist interpersonal skills: A five-year longitudinal study of a therapist assessment protocol.

OBJECTIVE: In the past decade, variation in outcomes between therapists (i.e., therapist effects) have become increasingly recognized as an important factor in psychotherapy. Less is known, however, about what accounts for differences between therapists. The present study investigates the possibility that therapists' basic therapy-related interpersonal skills may impact outcomes. METHOD: To examine this, psychotherapy postgraduate trainees completed both an observer- and an expert-rated behavioral assessment: the Therapy-Related Interpersonal Behaviors (TRIB). TRIB scores were used to predict trainees' outcomes over the course of the subsequent five years. RESULTS: Results indicate that trainees' with more positively rated interpersonal behaviors assessed in the observer-rated group format but not in a single expert-rated format showed superior outcomes over the five-year period. This effect remained controlling for therapist characteristics (therapist gender, theoretical orientation [cognitive behavioral or psychodynamic], amount of supervision, patient's order within therapist's caseload), and patient characteristics (patient age, gender, number of comorbid diagnoses, global severity, and personality disorder diagnosis). CONCLUSIONS: These findings underscore the importance of therapists' interpersonal skills as a predictor of outcome and source of therapist effects. The potential utility of assessing therapists' and therapists-in-training interpersonal skills are discussed.

Interactions of donor sources and media influence the histo-morphological quality of full-thickness skin models.

Human artificial skin models are increasingly employed as non-animal test platforms for research and medical purposes. However, the overall histopathological quality of such models may vary significantly. Therefore, the effects of manufacturing protocols and donor sources on the quality of skin models built-up from fibroblasts and keratinocytes derived from juvenile foreskins is studied. Histo-morphological parameters such as epidermal thickness, number of epidermal cell layers, dermal thickness, dermo-epidermal adhesion and absence of cellular nuclei in the corneal layer are obtained and scored accordingly. In total, 144 full-thickness skin models derived from 16 different donors, built-up in triplicates using three different culture conditions were successfully generated. In univariate analysis both media and donor age affected the quality of skin models significantly. Both parameters remained statistically significant in multivariate analyses. Performing general linear model analyses we could show that individual medium-donor-interactions influence the quality. These observations suggest that the optimal choice of media may differ from donor to donor and coincides with findings where significant inter-individual variations of growth rates in keratinocytes and fibroblasts have been described. Thus, the consideration of individual medium-donor-interactions may improve the overall quality of human organ models thereby forming a reproducible test platform for sophisticated clinical research.

A first vascularized skin equivalent as an alternative to animal experimentation.

Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.

[Latent classes of personality disorders: group comparisons and course of psychotherapy]. / Latente Klassen von Persönlichkeitsstörungen: Gruppenvergleiche und Psychotherapieverläufe.

Using latent class analysis the Personality Disorder Screening (PDS) classifies patients into 4 groups: personality disordered (PD) patients (PDS+), healthy patients (PDS -) and 2 hybrid classes with exaggerated personality styles (histrionic/dependent and avoidant/obsessive-compulsive). The present study investigated if the PDS groups differ concerning sociodemographic and clinical variables, psychological distress and treatment outcome. We analyzed the PDS response patterns of 555 outpatients. PDS+ group membership is associated with typical PD characteristics, chronic depression and a high level of general psychological distress. Patients of both hybrid classes are found to show average psychological distress. The treatment was effective for all patients. Membership in the histrionic/dependent hybrid class is associated with early drop out from outpatient therapy.